Stat3 and CCAAT enhancer-binding protein β (C/ebpβ) activate Fanconi C gene transcription during emergency granulopoiesis

Chirag A. Shah, Larisa Broglie, Liping Hu, Ling Bei, Weiqi Huang, Danielle B. Dressler, Elizabeth A Eklund*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Interferon consensus sequence-binding protein (Icsbp) is required for terminating emergency granulopoiesis, an episodic event responsible for granulocyte production in response to infections and a key component of the innate immune response. Icsbp inhibits the expression of Stat3 and C/ebpβ, transcription factors essential for initiating and sustaining granulopoiesis, and activates transcription of FanconiC(FANCC), aDNArepair protein. In prior studies, we noted accelerated bone marrow failure in Fancc-/-mice undergoing multiple episodes of emergency granulopoiesis, associated with apoptosis of bone marrow cells with unrepaired DNA damage. Additionally, we found increased expression of Fanconi C and F proteins during emergency granulopoiesis. These findings suggest that Icsbp protects the bone marrow fromDNAdamage by increasing activity of the Fanconi DNA repair pathway, but the mechanisms for FANCC activation during initiation of emergency granulopoiesis are unclear. In this study, we observed that Stat3 and C/ebpβ activate FANCC transcription and contribute to DNA repair. Our findings indicate that FancC expression is increased during Stat3-and C/ebpβ-induced initiation of emergency granulopoiesis by these transcription factors and is maintained through termination by Icsbp. Our work reveals that Stat3-and C/ebpβ-mediated FancC expression is a critical component for initiating and sustaining key innate immune responses.

Original languageEnglish (US)
Pages (from-to)3937-3948
Number of pages12
JournalJournal of Biological Chemistry
Volume293
Issue number11
DOIs
StatePublished - Mar 16 2018

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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